Targeting Lewis Y (Le(y)) in small cell lung cancer with a humanized monoclonal antibody, hu3S193: A pilot trial testing two dose levels Journal Article

  

Authors:	Krug, L. M.; Milton, D. T.; Jungbluth, A. A.; Chen, L. C.; Quaia, E.; Pandit-Taskar, N.; Nagel, A.; Jones, J.; Kris, M. G.; Finn, R.; Smith-Jones, P.; Scott, A. M.; Old, L.; Divgi, C.
Article Title:	Targeting Lewis Y (Le(y)) in small cell lung cancer with a humanized monoclonal antibody, hu3S193: A pilot trial testing two dose levels
Abstract:	INTRODUCTION: Lewis Y (Le) is a blood group antigen with robust expression on the surface of epithelial tumors, including small cell lung cancer (SCLC), making it a potential target for antibody-based immunotherapy. 3S193, an immunoglobulin G3 monoclonal antibody, has demonstrated superior specificity, affinity, and cytotoxicity over other anti-Le antibodies. A phase I trial of humanized 3S193 (hu3S193) with dosing up to 40 mg/m demonstrated tumor targeting without serious toxicities or the development of human anti-human antibodies. METHODS: We tested the targeting and pharmacokinetics of hu3S193 in patients with SCLC. Eligibility required progressive SCLC treated with up to three previous chemotherapy regimens, measurable disease not previously irradiated, and tumor samples positive for 3S193 by immunohistochemistry. Patients received four weekly injections of hu3S193, five patients at 10 mg/m and five patients at 20 mg/m. The first and fourth injections were radiolabeled with indium-111 for gamma camera imaging. RESULTS: Of 40 patients screened, 25 of 34 (74%) assessable SCLC tumor samples were 3S193 positive by immunohistochemistry. Ten patients were treated with hu3S193; nine completed all four injections. All fluorodeoxyglucose (FDG)-avid lesions >2 cm were visualized on antibody single-photon emission computed tomography. Some lesions overlying vascular structures could not be visualized. No difference was noted in imaging or pharmacokinetics between the first and fourth injections. Toxicities included grade 2 urticaria (n = 1), grade 1 vomiting (n = 2), and grade 2 hypertension (n = 1) transiently after infusion at the higher dose. CONCLUSIONS: Given the strong tumor targeting, particularly at the higher dose, the favorable toxicity profile, and the potential for immunomodulatory effects, hu3S193 warrants further investigation in SCLC. © 2007International Association for the Study of Lung Cancer.
Keywords:	immunohistochemistry; adult; clinical article; controlled study; human tissue; treatment outcome; treatment response; aged; bone neoplasms; middle aged; unclassified drug; clinical trial; advanced cancer; hypertension; liver neoplasms; drug targeting; cancer patient; brain neoplasms; antigen expression; cancer immunotherapy; controlled clinical trial; lung neoplasms; cancer screening; time factors; monoclonal antibody; tissue section; chemotherapy induced emesis; lung small cell cancer; antibodies, monoclonal; indium radioisotopes; isotope labeling; tissue distribution; pilot projects; immunomodulation; therapy effect; screening test; radioimmunotherapy; single photon emission computer tomography; indium 111; fluorodeoxyglucose; urticaria; small cell lung cancer; lewis blood-group system; carcinoma, small cell; scintillation camera; blood group lewis system; hu3s193; lewis y; monoclonal antibody hu 3s193
Journal Title:	Journal of Thoracic Oncology
Volume:	2
Issue:	10
ISSN:	1556-0864
Publisher:	Elsevier Inc.
Date Published:	2007-10-01
Start Page:	947
End Page:	952
Language:	English
DOI:	10.1097/JTO.0b013e3181560dcc
PUBMED:	17909358
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34848863393&partnerID=40&md5=80c4b779d19a22a8549ddb16ecf1c8d0
Notes:	--- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "Source: Scopus"

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